Fig. 6

Simplified overview of ISG regulation by STAT1 and STAT2 in BCR-ABL- and JAK2V617F-positive cells. In BCR-ABL-expressing cells, STAT2 is partially phosphorylated leading to ISG repression [43] and is not capable to induce STAT1 expression. In addition, chromatin marks negatively regulating gene expression are present (i.e., H3K27me3). STAT2, although not phosphorylated in JAK2V617F-positive cells, can induce STAT1 expression in the presence of histone marks representing active promoters (i.e., H3K9ac and H3K27ac). Upon stimulation with IFNa, STAT2 is essential for STAT1 phosphorylation at its tyrosine residue Y701 in BCR-ABL-positive cells (indicated by red arrow). The ISGF3 complex is formed and ISG expression is induced. IFNa stimulation of JAK2V617F-positive cells leads to ISGF3 complex formation and ISG as well as STAT1 promoter access. The equilibrium of STAT1/STAT1 and STAT1/STAT3 dimers shifts in dependence of the amount of active STAT2. STAT1/3 illustrates different dimer options: STAT1/STAT1, STAT1/STAT3, and STAT3/STAT3. In BCR-ABL-expressing cells, STAT3 is phosphorylated after IFNa binding to its receptor. P, tyrosine phosphorylation